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7zg0
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Murine IL-27 in complex with IL-27Ra and a non-competing Nb== | |
| + | <StructureSection load='7zg0' size='340' side='right'caption='[[7zg0]], [[Resolution|resolution]] 3.18Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7zg0]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZG0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.18Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7zg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zg0 OCA], [https://pdbe.org/7zg0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zg0 RCSB], [https://www.ebi.ac.uk/pdbsum/7zg0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zg0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/IL27A_MOUSE IL27A_MOUSE] Associates with EBI3 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive but not memory CD4 T-cells. It also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR which appears to be required but not sufficient for IL-27-mediated signal transduction. IL-27 potentiate the early phase of TH1 response and suppress TH2 and TH17 differentiation. It induces the differentiation of TH1 cells via two distinct pathways, p38 MAPK/TBX21- and ICAM1/ITGAL/ERK-dependent pathways. It also induces STAT1, STAT3, STAT4 and STAT5 phosphorylation and activates TBX21/T-Bet via STAT1 with resulting IL12RB2 up-regulation, an event crucial to TH1 cell commitment. It suppresses the expression of GATA3, the inhibitor TH1 cells development. In CD8 T-cells, it activates STATs as well as GZMB. IL-27 reveals to be a potent inhibitor of TH17 cell development and of IL-17 production. Indeed IL27 alone is also able to inhibit the production of IL17 by CD4 and CD8 T-cells. While IL-27 suppressed the development of pro-inflammatory Th17 cells via STAT1, it inhibits the development of anti-inflammatory inducible regulatory T-cells, iTreg, independently of STAT1. IL-27 has also an effect on cytokine production, it suppresses pro-inflammatory cytokine production such as IL2, IL4, IL5 and IL6 and activates suppressors of cytokine signaling such as SOCS1 and SOCS3. Apart from suppression of cytokine production, IL-27 also antagonizes the effects of some cytokines such as IL6 through direct effects on T-cells. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines such as IP-10/CXCL10 and MIG/CXCL9.<ref>PMID:12121660</ref> <ref>PMID:14565860</ref> <ref>PMID:14657353</ref> <ref>PMID:14871851</ref> <ref>PMID:15585838</ref> <ref>PMID:15688376</ref> <ref>PMID:16034109</ref> <ref>PMID:16365415</ref> <ref>PMID:16493033</ref> <ref>PMID:16751375</ref> <ref>PMID:16906166</ref> <ref>PMID:16906167</ref> <ref>PMID:17015723</ref> <ref>PMID:17114427</ref> <ref>PMID:17549733</ref> | ||
| - | + | ==See Also== | |
| - | + | *[[Interleukin 3D structures|Interleukin 3D structures]] | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: Savvides | + | </StructureSection> |
| - | [[Category: | + | [[Category: Lama glama]] |
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Bloch Y]] | ||
| + | [[Category: Savvides SN]] | ||
| + | [[Category: Skladanowska K]] | ||
Current revision
Murine IL-27 in complex with IL-27Ra and a non-competing Nb
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